Mice homozygous for the targeted mutation are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. No endogenous gene product is detectable in splenocyte supernatants. Mutant mice crossed to the DBA/1LacJ background (I-Aq haplotype) are susceptible to collagen-induced arthritis. Deletion of the endogenous gene exacerbates both the incidence and severity of collagen-induced arthritis, which is accompanied with increased IgG2 and decreased IgG1 in sera. Following type II collagen (CII) tolerization of mutant mice, splenocytes cultured with CII have increased Th2 (IL-5, IL-9, IL-10, IL-13) and Th1 (IFNgamma, IL-6) cytokines. Mutant mice may be useful in other studies of collagen-induced arthritis, rheumatoid arthritis, mechanisms of tolerance, regulation of autoimmune disease, and T helper cell immune responses.
On the C57BL/6 background (see Stock No. 002253) from which this mouse was created, T and B cell development is normal but IgGl and IgE levels and the ability of homozygous mutant mice to produce Th2-derived cytokines are significantly reduced.
